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Morphological and Functional Correlations in Acute Central Serous Chorioretinopathy

Doc Ophthalmol. 2024 Mar 18. doi: 10.1007/s10633-024-09969-8. Online ahead of print.

ABSTRACT

PURPOSE: We evaluate morphological and functional correlations in patients with acute central serous chorioretinopathy (CSC).

METHODS: A prospective study was conducted on 50 patients with an acute CSC episode lasting less than 3 months. At baseline, assessments included optical coherence tomography (OCT), best-corrected visual acuity (BCVA), contrast sensitivity (CS), microperimetry (MP), and multifocal electroretinography (mfERG). A correlation analysis between OCT morphological parameters (maximal subretinal fluid height (SRF), central retinal thickness (CRT), and macular volume (MV)) and functional parameters was conducted on the affected eye for each patient.

RESULTS: Among the morphological parameters, SRF showed the strongest correlations with functional parameters (r absolute value range = 0.10-0.70). Weak correlations were observed between BCVA and morphological parameters (r absolute value range = 0.14-0.26). Average retinal sensitivity (MP-A) was the functional parameter displaying the most robust negative correlation with morphological parameters (r absolute value range = 0.61-0.70). In contrast, average contrast sensitivity (CS-A) and mfERG average amplitude density in the first (mfERG-A1) and second (mfERG-A2) ring showed weak to moderate (r absolute value range = 0.35-0.56) yet statistically significantly nonzero correlations.

CONCLUSIONS: SRF and CRT could serve as the most representative morphological proxies for visual function deficit in acute CSC patients. Retinal sensitivity, as measured by MP, may be superior to BCVA in clinical research studies or when an in-depth visual function evaluation is needed.

PMID:38498077 | DOI:10.1007/s10633-024-09969-8

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Objective demonstration of eyelid spasm relief with smartphone and custom software in hemifacial spasm patients

Int Ophthalmol. 2024 Mar 18;44(1):144. doi: 10.1007/s10792-024-03070-4.

ABSTRACT

PURPOSE: To objectively demonstrate eyelid spasms relief in hemifacial spasm (HFS) patients using a smartphone and a custom-made software.

METHODS: Nineteen patients with HFS had standardized videos recorded with a smartphone (iPhone 6S, Apple) camera before and 15 days after receiving onabotulinumtoxinA injections. Nineteen age-matched control subjects were also assessed. The Eye Aspect Ratio (EAR) is an algorithm previously described to determine whether the eye is opened or closed. When the eye is closed, EAR tends to be closer to zero. Analogously, if the eye is wide open, values are greater. A custom-made software using the EAR concept was developed and pre- and post-treatment EARs were analyzed to assess HFS patients.

RESULTS: Botulinum toxin (BoNT) injections led to a significant increase in the average EAR of the affected side: + 10.4% (p = 0.0175) of HFS patients, compared to baseline. Mean EAR before BoNT applications were significantly lower (16.2%) on the affected side (0.25 ± 0.05) of HFS patients when compared to controls (0.30 ± 0.05, p = 0.004). After BoNT injections, no statistically significant difference was observed for the average EAR between the affected side of HFS patients (0.27 ± 0.04) and controls (p = 0.20).

CONCLUSIONS: Use of a smartphone and custom-made software objectively demonstrated eyelid spasm relief in patients with HFS. Additional refinement of this system could permit more accurate assessments of treatment response rates for each patient, making it possible to be used in clinical practice.

PMID:38498055 | DOI:10.1007/s10792-024-03070-4

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Association Between Physical Activity and the Risk of Burnout in Health Care Workers: Systematic Review

JMIR Public Health Surveill. 2024 Mar 18;10:e49772. doi: 10.2196/49772.

ABSTRACT

BACKGROUND: Burnout is a multidimensional psychological syndrome that arises from chronic workplace stress. Health care workers (HCWs), who operate in physically and emotionally exhausting work contexts, constitute a vulnerable group. This, coupled with its subsequent impact on patients and public economic resources, makes burnout a significant public health concern. Various self-care practices have been suggested to have a positive effect on burnout among HCWs. Of these, physical activity stands out for its ability to combine psychological, physiological, and biochemical mechanisms. In fact, it promotes psychological detachment from work and increases self-efficacy by inhibiting neurotransmitters and neuromodulators, increasing endorphin levels, enhancing mitochondrial function, and attenuating the hypothalamic pituitary-adrenal axis response to stress.

OBJECTIVE: Our objective was to conduct a systematic review of the evidence on the association between physical activity and burnout among HCWs.

METHODS: We considered HCWs, physical activity, and burnout, framing them as population, exposure, and outcome, respectively. We searched APA PsycArticles, MEDLINE, and Scopus until July 2022. We extracted relevant data on study design, methods to measure exposure and outcome, and statistical approaches.

RESULTS: Our analysis encompassed 21 independent studies. Although 10% (2/21) of the studies explicitly focused on physical activity, the remaining investigations were exploratory in nature and examined various predictors, including physical activity. The most commonly used questionnaire was the Maslach Burnout Inventory. Owing to the heterogeneity in definitions and cutoffs used, the reported prevalence of burnout varied widely, ranging from 7% to 83%. Heterogeneity was also observed in the measurement tools used to assess physical activity, with objective measures rarely used. In total, 14% (3/21) of the studies used structured questionnaires to assess different types of exercise, whereas most studies (18/21, 86%) only recorded the attainment of a benchmark or reported the frequency, intensity, or duration of exercise. The reported prevalence of physically active HCWs ranged from 44% to 87%. The analyses, through a variety of inferential approaches, indicated that physical activity is often associated with a reduced risk of burnout, particularly in the domains of emotional exhaustion and depersonalization. Furthermore, we compiled and classified a list of factors associated with burnout.

CONCLUSIONS: Our comprehensive overview of studies investigating the association between physical activity and burnout in HCWs revealed significant heterogeneity in definitions, measurements, and analyses adopted in the literature. To address this issue, it is crucial to adopt a clear definition of physical activity and make thoughtful choices regarding measurement tools and methodologies for data analysis. Our considerations regarding the measurement of burnout and the comprehensive list of associated factors have the potential to improve future studies aimed at informing decision-makers, thus laying the foundation for more effective management measures to address burnout.

PMID:38498040 | DOI:10.2196/49772

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Improving Women’s Health Across the Life Span-JAMA Internal Medicine Call for Papers

JAMA Intern Med. 2024 Mar 18. doi: 10.1001/jamainternmed.2024.0136. Online ahead of print.

NO ABSTRACT

PMID:38497973 | DOI:10.1001/jamainternmed.2024.0136

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Magnetic Resonance Imaging Characteristics of LGI1-Antibody and CASPR2-Antibody Encephalitis

JAMA Neurol. 2024 Mar 18. doi: 10.1001/jamaneurol.2024.0126. Online ahead of print.

ABSTRACT

IMPORTANCE: Rapid and accurate diagnosis of autoimmune encephalitis encourages prompt initiation of immunotherapy toward improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis, and awaiting autoantibody results can delay immunotherapy.

OBJECTIVE: To identify simple magnetic resonance imaging (MRI) characteristics that accurately distinguish 2 common forms of autoimmune encephalitis, LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD).

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study involved a retrospective, blinded analysis of the first available brain MRIs (taken 2000-2022) from 192 patients at Oxford University Hospitals in the UK and Mayo Clinic in the US. These patients had LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings were validated in an independent cohort by 3 neurologists (n = 105). Groups were statistically compared with contingency tables. Data were analyzed in 2023.

MAIN OUTCOMES AND MEASURES: MRI findings including T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensities, swelling or volume loss, presence of gadolinium contrast enhancement, and diffusion-weighted imaging changes. Correlations with clinical features.

RESULTS: Among 192 participants with MRIs reviewed, 71 were female (37%) and 121 were male (63%); the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and/or FLAIR hyperintensities were less likely to extend outside the temporal lobe (3/42 patients [7%] vs 17/18 patients [94%] with VE; P < .001, and 3/4 patients [75%] with CJD; P = .005), less frequently exhibited swelling (12/55 [22%] with LGI1/CASPR2-Ab-E vs 13/22 [59%] with VE; P = .003), and showed no diffusion restriction (0 patients vs 16/22 [73%] with VE and 8/10 [80%] with CJD; both P < .001) and rare contrast enhancement (1/20 [5%] vs 7/17 [41%] with VE; P = .01). These findings were validated in an independent cohort and generated an area under the curve of 0.97, sensitivity of 90%, and specificity of 95% among cases with T2/FLAIR hyperintensity in the hippocampus and/or amygdala.

CONCLUSIONS AND RELEVANCE: In this study, T2 and/or FLAIR hyperintensities confined to the temporal lobes, without diffusion restriction or contrast enhancement, robustly distinguished LGI1/CASPR2-Ab-E from key differential diagnoses. These observations should assist clinical decision-making toward expediting immunotherapy. Their generalizability to other forms of autoimmune encephalitis and VE should be examined in future studies.

PMID:38497971 | DOI:10.1001/jamaneurol.2024.0126

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Nevin Manimala Statistics

Lymph Node Isolated Tumor Cells in Patients With Endometrial Cancer

JAMA Netw Open. 2024 Mar 4;7(3):e240988. doi: 10.1001/jamanetworkopen.2024.0988.

ABSTRACT

IMPORTANCE: Isolated tumor cells (ITCs) are the histopathological finding of small clusters of cancer cells no greater than 0.2 mm in diameter in the regional lymph nodes. For endometrial cancer, the prognostic significance of ITCs is uncertain.

OBJECTIVE: To assess clinico-pathological characteristics and oncologic outcomes associated with ITCs in endometrial cancer.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study using the National Cancer Database included patients with endometrial cancer who had primary hysterectomy and nodal evaluation from 2018 to 2020. Patients with microscopic and macroscopic nodal metastases and distant metastases were excluded. Data were analyzed from June to September 2023.

EXPOSURE: Regional nodal status with ITCs (N0[i+] classification) or no nodal metastasis (N0 classification).

MAIN OUTCOMES AND MEASURES: (1) Clinical and tumor characteristics associated with ITCs, assessed with multivariable binary logistic regression model, and (2) overall survival (OS) associated with ITCs, evaluated by nonproportional hazard analysis with restricted mean survival time at 36 months.

RESULTS: A total of 56 527 patients were included, with a median (IQR) age of 64 (57-70) years. The majority had T1a lesion (37 836 [66.9%]) and grade 1 or 2 endometrioid tumors (40 589 [71.8%]). ITCs were seen in 1462 cases (2.6%). In a multivariable analysis, ITCs were associated with higher T classification, larger tumor size, lymphovascular space invasion (LVSI), and malignant peritoneal cytology. Of those tumor factors, LVSI had the largest association with ITCs (7.9% vs 1.4%; adjusted odds ratio [aOR], 4.37; 95% CI, 3.87-4.93), followed by T1b classification (5.3% vs 1.3%; aOR, 2.62; 95% CI, 2.30-2.99). At the cohort level, 24-month OS rates were 94.3% (95% CI, 92.4%-95.7%) for the ITC group and 96.1% (95% CI, 95.9%-96.3%) for the node-negative group, and the between-group difference in expected mean OS time at 36 months was 0.35 (SE, 0.19) months, but it was not statistically significant (P = .06). There was a statistically significant difference in OS when the low-risk group (stage IA, grade 1-2 endometrioid tumors with no LVSI) was assessed per nodal status and adjuvant therapy use (P < .001): (1) among the cases treated with surgical therapy alone, 24-month OS rates were 95.9% (95% CI, 89.5%-98.5%) for the ITC group and 98.8% (95% CI, 98.6%-99.0%) for the node-negative group, and the between-group mean OS time difference at 36 months was 0.61 (SE, 0.43) months (P = .16); and (2) among the cases with ITCs, adjuvant therapy (radiotherapy alone, systemic chemotherapy alone, or both) was associated with improved survival compared with no adjuvant therapy (24-month OS rates, 100% vs 95.9%; between-group mean OS time difference at 36 months, 0.95 [SE, 0.43] months; P = .03).

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with surgically staged endometrial cancer, the results of exploratory analysis suggested that presence of ITCs in the regional lymph node may be associated with OS in the low-risk group. While adjuvant therapy was associated with improved OS in the low-risk group with ITCs, careful interpretation is necessary given the favorable outcomes regardless of adjuvant therapy use. This hypothesis-generating observation in patients with low-risk endometrial cancer warrants further investigation, especially with prospective setting.

PMID:38497964 | DOI:10.1001/jamanetworkopen.2024.0988

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Prison Buprenorphine Implementation and Postrelease Opioid Use Disorder Outcomes

JAMA Netw Open. 2024 Mar 4;7(3):e242732. doi: 10.1001/jamanetworkopen.2024.2732.

ABSTRACT

IMPORTANCE: Agonist medications for opioid use disorder (MOUD), buprenorphine and methadone, in carceral settings might reduce the risk of postrelease opioid overdose but are uncommonly offered. In April 2019, the Massachusetts Department of Correction (MADOC), the state prison system, provided buprenorphine for incarcerated individuals in addition to previously offered injectable naltrexone.

OBJECTIVE: To evaluate postrelease outcomes after buprenorphine implementation.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study with interrupted time-series analysis used linked data across multiple statewide data sets in the Massachusetts Public Health Data Warehouse stratified by sex due to differences in carceral systems. Eligible participants were individuals sentenced and released from a MADOC facility to the community. The study period for the male sample was January 2014 to November 2020; for the female sample, January 2015 to October 2019. Data were analyzed between February 2022 and January 2024.

EXPOSURE: April 2019 implementation of buprenorphine during incarceration.

MAIN OUTCOMES AND MEASURES: Receipt of MOUD within 4 weeks after release, opioid overdose, and all-cause mortality within 8 weeks after release, each measured as a percentage of monthly releases who experienced the outcome. Segmented linear regression analyzed changes in outcome rates after implementation.

RESULTS: A total of 15 225 individuals were included. In the male sample there were 14 582 releases among 12 688 individuals (mean [SD] age, 35.0 [10.8] years; 133 Asian and Pacific Islander [0.9%], 4079 Black [28.0%], 4208 Hispanic [28.9%], 6117 White [41.9%]), a rate of 175.7 releases per month; the female sample included 3269 releases among 2537 individuals (mean [SD] age, 34.9 [9.8] years; 328 Black [10.0%], 225 Hispanic [6.9%], 2545 White [77.9%]), a rate of 56.4 releases per month. Among male participants at 20 months postimplementation, the monthly rate of postrelease buprenorphine receipt was higher than would have been expected under baseline trends (21.2% vs 10.6% of monthly releases; 18.6 additional releases per month). Naltrexone receipt was lower than expected (1.0% vs 6.0%; 8.8 fewer releases per month). Monthly rates of methadone receipt (1.4%) and opioid overdose (1.8%) were not significantly different than expected. All-cause mortality was lower than expected (1.9% vs 2.8%; 1.5 fewer deaths per month). Among female participants at 7 months postimplementation, buprenorphine receipt was higher than expected (31.6% vs 9.5%; 12.4 additional releases per month). Naltrexone receipt was lower than expected (3.4% vs 7.2%) but not statistically significantly different. Monthly rates of methadone receipt (1.1%), opioid overdose (4.8%), and all-cause mortality (1.6%) were not significantly different than expected.

CONCLUSIONS AND RELEVANCE: In this cohort study of state prison releases, postrelease buprenorphine receipt increased and naltrexone receipt decreased after buprenorphine became available during incarceration.

PMID:38497959 | DOI:10.1001/jamanetworkopen.2024.2732

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Text vs Patient Portal Messaging to Improve Influenza Vaccination Coverage: A Health System-Wide Randomized Clinical Trial

JAMA Intern Med. 2024 Mar 18. doi: 10.1001/jamainternmed.2024.0001. Online ahead of print.

ABSTRACT

IMPORTANCE: Increasing influenza vaccination rates is a public health priority. One method recommended by the US Centers for Disease Control and Prevention and others is for health systems to send reminders nudging patients to be vaccinated.

OBJECTIVE: To evaluate and compare the effect of electronic health record (EHR)-based patient portal reminders vs text message reminders on influenza vaccination rates across a health system.

DESIGN, SETTING, AND PARTICIPANTS: This 3-arm randomized clinical trial was conducted from September 7, 2022, to April 30, 2023, among primary care patients within the University of California, Los Angeles (UCLA) health system.

INTERVENTIONS: Arm 1 received standard of care. The health system sent monthly reminder messages to patients due for an influenza vaccine by portal (arm 2) or text (arm 3). Arm 2 had a 2 × 2 nested design, with fixed vs responsive monthly reminders and preappointment vs no preappointment reminders. Arm 3 had 1 × 2 design, with preappointment vs no preappointment reminders. Preappointment reminders for eligible patients were sent 24 and 48 hours before scheduled primary care visits. Fixed reminders (in October, November, and December) involved identical messages via portal or text. Responsive portal reminders involved a September message asking patients about their plans for vaccination, with a follow-up reminder if the response was affirmative but the patient was not yet vaccinated.

MAIN OUTCOMES AND MEASURES: The primary outcome was influenza vaccination by April 30, 2023, obtained from the UCLA EHR, including vaccination from pharmacies and other sources.

RESULTS: A total of 262 085 patients (mean [SD] age, 45.1 [20.7] years; 237 404 [90.6%] adults; 24 681 [9.4%] children; 149 349 [57.0%] women) in 79 primary care practices were included (87 257 in arm 1, 87 478 in arm 2, and 87 350 in arm 3). At the entire primary care population level, none of the interventions improved influenza vaccination rates. All groups had rates of approximately 47%. There was no statistical or clinically significant improvement following portal vs text, preappointment reminders vs no preappointment reminders (portal and text reminders combined), or responsive vs fixed monthly portal reminders.

CONCLUSIONS AND RELEVANCE: At the population level, neither portal nor text reminders for influenza vaccination were effective. Given that vaccine hesitancy may be a major reason for the lack of impact of portal or text reminders, more intensive interventions by health systems are needed to raise influenza vaccination coverage levels.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05525494.

PMID:38497955 | DOI:10.1001/jamainternmed.2024.0001

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The quest for down scale representativeness: how to exploit CFD to design a shear study for vaccines

Pharm Dev Technol. 2024 Mar 18:1-17. doi: 10.1080/10837450.2024.2331243. Online ahead of print.

ABSTRACT

In this work we exploit Computational Fluid Dynamics (CFD) to evaluate Stirred Tank Reactor (STR) Process Engineer Parameters (PEP) and design a scale down system (SDS) to be representative of the formulation and filling process steps for an Aluminum adjuvanted vaccine Drug Product (DP). To study the shear history in the SDS we used the concept of number of passages, combined with an appropriate stirring speed down scale strategy comprising of either i) Tip speed equivalence, widely used as scale-up criterion for shear-sensitive product, or ii) Rotating shear, a shear metric introduced by Metz and Otto in 1957 but never used as scaling criterion. The outcome of the CFD simulations shows that the tip equivalence generates a worst case SDS in terms of shear, whereas the rotating shear scaling approach could be used to design more representative SDS. We monitored the trend over time for “In Vitro Relative Potency” as DP Critical Quality Attribute for both scaling approaches, which highlighted the crucial role of choosing the appropriate scaling down approach to be representative of the manufacturing scale during process characterization studies.

PMID:38497925 | DOI:10.1080/10837450.2024.2331243

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Tocilizumab treatment in COVID-19 patients: therapy’s side effects and effect on mortality

Eur Rev Med Pharmacol Sci. 2024 Mar;28(5):2107-2116. doi: 10.26355/eurrev_202403_35623.

ABSTRACT

OBJECTIVE: This study aimed to determine the effect of tocilizumab use on mortality and the potential side effects in COVID-19 patients.

PATIENTS AND METHODS: The intensive care patients were divided into the tocilizumab group and the control group. Hemogram, biochemistry, acute phase reactant values, age, gender, comorbidity, and culture results were recorded on the 0th, 3rd, 7th, and 14th days. Factors affecting mortality between and within the groups and side effects were examined.

RESULTS: 32.14% of the patients were female, and 67.85% were male. The tocilizumab group had high alanine aminotransferase and potassium on day 3. On day 7, low levels of platelet, glucose, international normalized ratio, prothrombin time, and active partial thromboplastin time levels were observed. Procalcitonin, C-reactive protein, and fibrinogen levels were low on days 3 and 7. The relationship between the tocilizumab treatment and mortality was statistically not significant, although the APACHE score was low. In the tocilizumab group, the presence of additional disease and reproduction in culture significantly increased mortality.

CONCLUSIONS: Despite the risks of side effects, tocilizumab was used in COVID-19 treatment since it is an interleukin-6 blocker. Although the first publications stated that the treatment could decrease the mortality rate, later meta-analyses did not support these results. Our study also found that using tocilizumab did not make a difference in long-term mortality. We also observed that the known side effects were seen in short-term use.

PMID:38497892 | DOI:10.26355/eurrev_202403_35623